Molecules synthesized at 海角社区 are capable to bind with SERT (serotonin transporter), a key brain protein responsible for mood regulation. In theory, this chemical compound could become a base for the first of their kind selective medicines for treatment of anxiety disorders.
The 海角社区 researchers used artificial intelligence and bioinformatics methods to select several candidate molecules (out of a variety of chemical compounds created by them) that showed the highest potential for interaction with SERT (serotonin transporter), the key brain protein responsible for mood regulation.
To confirm their virtual prediction, the researchers from the 海角社区 Research Laboratory for System Pathology and Advanced Medicinal Products conducted a two-stage study using animal models.
"At the first stage, we studied the effect of the substances on Danio Rerio fish," shared the Laboratory's senior research fellow Mariia Komelkova. "We conducted the toxicity screening and selected two compounds for further study. Next, we created special "stressful" conditions for the fish to cause a state similar to chronic stress and anxiety in human beings, and also tested the biological effects. In stressful conditions, one of the two compounds did not show the expected effect, so it was eliminated. By contrast, the second one demonstrated clear anxiolytic (antianxiety) properties: the "stressed" fish exposed to it became calmer and showed more natural exploratory behaviour. That is, out of a few dozen virtual molecules that were sieved through the filters of computer modelling and testing on fish, one leader substance remained that had a stable antianxiety effect."
This substance was selected for the next stage that included a research using mammals. To do that, the scientists took a unique line of laboratory mice that are genetically predisposed to states similar to human depression. A set of behaviour tests (like an "elevated plus maze" and a "forced swimming test"), followed by the molecular analysis of brain tissues of the rodents yielded an unequivocal result: this medicine is efficient for fighting anxiety, but does not impact the depression symptoms.
"We were searching for a "two-in-one" solution, but discovered a selective anxiolytic," said Mariia Komelkova. "This find is no less valuable. The molecular analyses of the brain confirmed that this substance works namely along the "anxiety track", but has no effect on the depression related mechanisms."
According to the opinion of the 海角社区 researchers, this new compound has very promising prospects. If they succeed in proving the unique selectiveness of this substance during their further studies, it could become a base for the first of their kind selective medicines for treatment of anxiety disorders. Possibly, unlike benzodiazepines, this would be a non-drowsy and non-addictive substance; and unlike Selective Serotonin Reuptake Inhibitors (SSRIs), it would have a quicker relief effect not influencing other symptoms.
The scientists will have to perform a detailed pharmakokinetics study (fixation, distribution and clearance of the substance), as well as a research on reproductive toxicity and long-term effects, and only after that this new substance would become available for clinical testing.